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At least 829 records · Page 46Linked to original sources
PubMed1985

Release of slow reacting substance (SRS) from human leucocytes by lymphokine.

A human histamine releasing lymphokine (histamine releasing factor, HRF) was studied for its ability to release slow reacting substance (SRS) alongside histamine from human leucocytes. HRF was found to release a substantial amount of SRS from human leucocytes. The SRS was identified by its slow contraction of isolated guinea pig ileum preparation in the presence of atropine and mepyramine, inhibition of this action by the SRS antagonist FPL 55712, the inhibition of its production by eicosa--5, 8, 11, 14--tetraynoic acid (ETYA) but not indomethacin, and a final confirmation by a radioimmunoassay for leukotriene C4 (LTC4). Amounts of SRS ranging from a few nanograms to about 180 ng (eqt LTD4) could be released from 10(8) leucocytes depending on the dose of HRF, and there is a good correlation between the amount of SRS produced and the percentage histamine release accompanying it. These findings suggest that the human lymphokine (HRF) may play an important role in acute hypersensitivity and inflammatory reactions in addition to its traditional role as mediator of delayed hypersensitivity reactions.

Animals↗
PubMed1983

Arachidonic acid metabolism in isolated aorta and lung of the rat: effects of dipyridamole, nifedipine, propranolol, hydralazine and verapamil.

Effects of some vasodilating (dipyridamole, nifedipine and verapamil) and antihypertensive (propranolol, hydralazine) drugs on arachidonic acid metabolism in isolated rat aorta and lung have been studied. Dipyridamole significantly increased the formation of PGI2 in aorta and lung. Nifedipine and verapamil decreased the formation of PGI2 in aorta, these drugs though significantly increased the formation of PGI2 in lung. Nifedipine showed no appreciable effect on the generation of TxA2 in rat aorta but in lung both nifedipine and verapamil reduced TxA2 formation though significantly only in the latter case. Dipyridamole showed no effect. The beneficial effect of dipyridamole, seems, at least in part, to be due to its ability to enhance the production of PGI2 both in the aorta and lung, and probably in other tissues as well. Nifedipine and verapamil may show their antianginal effect by a combined effect of enhanced PGI2 and reduced TxA2 formation in lung. In lung, whereas hydralazine reduced the formation of both PGI2 and TxA2, propranolol increased the formation of PGI2. Hydralazine reduced the formation of TxA2 and increased PGI2 formation in aorta. The effect of the drugs on the ability of rat aorta to inhibit collagen induced platelet aggregation of human blood platelets was also examined.

Animals↗
PubMed1983

Unsaturated fatty acids and platelet aggregation: in vitro study.

The effects of several cis and two trans fatty acids (elaidic and linoelaidic acids) - sodium salt and also in free acid form - on ADP-induced platelet aggregation were studied. The effects of the cis and trans fatty acids (sod. salt) on collagen-induced aggregation were also examined. Besides, the effects of several cis fatty acids, including dihomo-gamma-linolenic acid, on arachidonic acid induced aggregation were examined. The results indicate that unsaturated fatty acids inhibit platelet aggregation induced by ADP and collagen. The unsaturated fatty acids, however, with most blood samples did not show any antiaggregation effect on arachidonic acid-induced aggregation. While showing an antiaggregation effect on collagen-induced aggregation and failing to do so on arachidonic acid-induced aggregation, this difference in the behaviour of the unsaturated fatty acids in the two aggregations can be explained on the basis of binding of exogenous test fatty acids to plasma proteins. The mechanism(s) by which unsaturated fatty acids, in general, may exert their antiaggregation effect is discussed.

Adenosine Diphosphate↗
PubMed1988

Teratology studies of compound LY171883 administered orally to rats and rabbits.

The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20. Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic.

Acetophenones↗
PubMed1990

Effects of chronic treatment with the leukotriene D4-antagonist compound LY171883 on B6C3F1 mice.

A 2-year toxicity/oncogenicity study was done to evaluate the potential effects of the leukotriene antagonist LY171883 in B6C3F1 mice. Dietary concentrations of LY171883 during the initial 7 months of the study were 0.0, 0.005, 0.015, or 0.05% but were increased to 0.0, 0.0075, 0.0225, or 0.075% during Months 7 through 24. The estimated average daily compound intake was 0.0, 7.3, 22.5, or 80.5 mg/kg for males and 0.0, 9.2, 27.5, or 95.9 mg/kg for females. Survival was not adversely affected by treatment, however, body weight of males and females in the high dose group was significantly lower than that of controls. The chronic toxicity was localized primarily to the liver. Liver weights were increased in males in the high dose group and in females in the mid and high dose groups. Microsomal p-nitroanisole-O-demethylase activity was increased in mid and high dose females. Hepatic peroxisomal beta-oxidation was increased approximately twofold in both sexes in the high dose group only. Centrilobular eosinophilic granular change of hepatocytes was a common histopathologic finding in male and female mice in the high dose group, with the incidence and severity being greater in females. An increased incidence of hepatocellular carcinomas was observed in female mice in the mid and high dose groups. The number of male mice in the high dose group with hepatocellular carcinomas was higher than that of controls but the change was not statistically significant. Hepatocellular adenomas were increased in females in the high dose group but not in males. All groups of treated females had increased nodular hepatocellular hyperplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗
PubMed1985

Towards a psychobiological model of cancer: biological considerations.

The control of tissue homeostasis is extremely complex and many factors contribute to the growth and development of tumours. Although the immune system has been regarded as an essential intermediary between putative psychological factors and the development or restraint of malignant tumours, this review indicates that many other possible mechanisms also exist. Current aspects of tumour biology, immunology and hormonal control systems are reviewed, and detailed psychobiological mediating mechanisms are considered at each stage of tumour development. An approach to the future investigation of this difficult field is proposed.

Autacoids↗
PubMed1995

Protective effect of peptide leukotriene antagonist on renal failure induced by a tourniquet in rabbits.

We studied the effects of a selective antagonist of peptide leukotriene D4/E4 (LY-171883) and 5-lipoxygenase inhibitor diethylcarbamazine (DEC) in renal failure induced by a tourniquet, because peptide leukotrienes (LTs) were suggested to play a key role in our previous study. The hind limbs of anesthetized rabbits were fastened for 5 h and then released for 6 h. LY171883 (4 mg/kg/h) and DEC (40 mg/kg/h) were administered via the aural vein from 30 min before the tourniquet and during the experiment in each tourniquet group. The tourniquet induced renal injuries represented by increases in serum BUN and creatinine, and the injuries in the fastened muscles represented increases in serum CPK and edema index of the fastened site. LY171883 and DEC significantly attenuated the aggravation of the renal functions induced by a tourniquet when compared with the vehicle-treated group. LY171883 did not affect the injuries in the fastened muscles, but DEC attenuated it significantly when compared with the vehicle-treated group. The protection of peptide LT antagonist and 5-lipoxygenase inhibitor in the tourniquet-induced renal failure elucidate that peptide LTs trigger renal failure induced by a tourniquet.

Acetophenones↗
PubMed1991

Effect of a novel 5-lipoxygenase inhibitor, E6080 on bronchospasm, airway cellular infiltration and leukotriene production in guinea pigs.

6-Hydroxy-2-(4-sulfamoylbenzylamino)-4,5,7-trimethylbenzothiazo le hydrochloride (E6080), an orally active and selective 5-lipoxygenase inhibitor, dose-dependently inhibited the bronchospasm induced by antigen (ovalbumin) inhalation in sensitized conscious guinea pigs. The inhibitory effect of E6080 was more potent than that of a typical 5-lipoxygenase inhibitor, AA861, but less than that of a leukotriene (LT) antagonist, LY171883. When airway infiltration of neutrophils and eosinophils was measured in bronchoalveolar lavage fluid (BALF) at 6 h after antigen inhalation by passively sensitized guinea pigs, the inhibitory effect of E6080 on neutrophil infiltration was more marked than that on eosinophil infiltration. The inhibitory effect of E6080 on bronchoalveolar cellular infiltration and bronchoepithelial damage was confirmed by examination of photomicrographs of the lung. In addition to the above pharmacological effects, E6080 inhibited the increase in BALF levels of both i-LTC4 and i-LTB4. These results suggest that E6080 may prove to be effective for the treatment of asthma, in which large amounts of leukotrienes (LTs) are elaborated.

Acetophenones↗
PubMed2001

Endogenous morphine and codeine. Possible role as endogenous anticonvulsants.

Exogenously administered morphine can have both convulsive or anticonvulsive effects, depending on the dose and species. The levels of the endogenous opiate alkaloids morphine and codeine were significantly elevated in specific rat brain regions by the convulsive drug, pentylenetetrazole, as well as by the anticonvulsant drugs, carbamazepine and phenytoin. Morphine and codeine levels in peripheral tissues (heart, lung, spleen and adrenal) were unaffected by these drugs. Maximal increases in morphine levels were seen in the hypothalamus and striatum (2-10-fold), while lesser increases occurred in the midbrain and brain stem (2-4-fold). Codeine levels were also markedly increased in hypothalamus (5-10 fold), In contrast to morphine, codeine levels were also increased in the hippocampus (2-10-fold), but were unchanged in the striatum. These studies suggest that the endogenous alkaloids morphine and codeine are involved in the modulation of convulsions and that morphine and/or codeine may act as an endogenous anticonvulsant.

Animals↗
PubMed1980

Fatty acid structural requirements for leukotriene biosynthesis.

Utilizing a variety of fatty acids, differing in chain length, degree and position of unsaturation, we investigated the substrate specificity for the enzymatic production of biologically active slow reacting substances (SRS) and of the other leukotrienes. A cell-free enzyme system obtained from RBL-1 cells was used in this study. The primary structural requirement observed for the conversion by this lipoxygenase enzyme system was a delta 5,8,11 unsaturation in a polyenoic fatty acid. Such fatty acids as 20:4 (5,8,11,14) 20:5 (5,8,11,14,17), 20:3 (5,8,11), 19:4 (5,8,11,14) and 18:4 (5,8,11,14) were readily converted to compounds that comigrated with 5-HETE and 5,12-DiHETE and to biologically active SRS. Chain length did not have an influence on the formatin of these hydroxyacids. Fatty acids with the initial unsaturation at delta 4, delta 6, delta 7, or delta 8 were a poor substrate for the leukotriene enzyme system. Therefore, this lipoxygenase pathway in leukocytes is quite different from the lipoxygenase in platelets which does not exhibit this specificity.

Animals↗